Multidentate 18F-Polypegylated Styrylpyridines As Imaging Agents for A尾 Plaques in Cerebral Amyloid Angiopathy (CAA)

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• 作者：Zhihao Zha ; Seok Rye Choi ; Karl Ploessl ; Brian P. Lieberman ; Wenchao Qu ; Franz Hefti ; Mark Mintun ; Daniel Skovronsky ; Hank F. Kung
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：December 8, 2011
• 年：2011
• 卷：54
• 期：23
• 页码：8085-8098
• 全文大小：587K
• 年卷期：v.54,no.23(December 8, 2011)
• ISSN：1520-4804

文摘

尾-Amyloid plaques (A尾 plaques) in the brain are associated with cerebral amyloid angiopathy (CAA). Imaging agents that could target the A尾 plaques in the living human brain would be potentially valuable as biomarkers in patients with CAA. A new series of ¹⁸F styrylpyridine derivatives with high molecular weights for selectively targeting A尾 plaques in the blood vessels of the brain but excluded from the brain parenchyma is reported. The styrylpyridine derivatives, 8a鈥?b>c, display high binding affinities and specificity to A尾 plaques (K_i = 2.87, 3.24, and 7.71 nM, respectively). In vitro autoradiography of [¹⁸F]8a shows labeling of 尾-amyloid plaques associated with blood vessel walls in human brain sections of subjects with CAA and also in the tissue of AD brain sections. The results suggest that [¹⁸F]8a may be a useful PET imaging agent for selectively detecting A尾 plaques associated with cerebral vessels in the living human brain.